期刊
JOURNAL OF MOLECULAR MEDICINE-JMM
卷 94, 期 8, 页码 943-955出版社
SPRINGER HEIDELBERG
DOI: 10.1007/s00109-016-1400-9
关键词
Hypoxia; Langerhans cells; Immunoregulatory receptors; Wounds
资金
- Italian Association for Cancer Research [10565, 9366, 15257, 121825]
- Italian Ministry of Health
- Fondazione Cariplo [2011-0463]
- European Network for Cancer Research in Children and Adolescents (ENCCA)
- Fondazione Umberto Veronesi
- Fondazione Ricerca Molinette Onlus
- Compagnia San Paolo (Progetti di Ricerca Ateneo)
- University of Torino
- Fondazione CRT
- Piedmont Foundation of Studies and Research on Burns Simone Teich Alasia
- Fondazione Angela Bossolasco
Langerhans cells (LCs) are a specialized dendritic cell subset that resides in the epidermis and mucosal epithelia and is critical for the orchestration of skin immunity. Recent evidence suggest that LCs are involved in aberrant wound healing and in the development of hypertrophic scars and chronic wounds, which are characterized by a hypoxic environment. Understanding LCs biology under hypoxia may, thus, lead to the identification of novel pathogenetic mechanisms of wound repair disorders and open new therapeutic opportunities to improve wound healing. In this study, we characterize a previously unrecognized role for hypoxia in significantly affecting the phenotype and functional properties of human monocyte-derived LCs, impairing their ability to stimulate naive T cell responses, and identify the triggering receptor expressed on myeloid (TREM)-1, a member of the Ig immunoregulatory receptor family, as a new hypoxia-inducible gene in LCs and an activator of their proinflammatory and Th1-polarizing functions in a hypoxic environment. Furthermore, we provide the first evidence of TREM-1 expression in vivo in LCs infiltrating hypoxic areas of active hypertrophic scars and decubitous ulcers, pointing to a potential pathogenic role of this molecule in wound repair disorders.
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